1. Field of the Invention
The present invention relates to methods and apparatus for therapeutically treating connective tissue and/or increasing vascularization in tissue using ultrasound. More particularly, the present invention relates to methods and apparatus which use ultrasound to stimulate growth or healing, or to treating and/or preventing pathologies of connective tissue, or to increase vascularization in ischaemic or grafted tissue using ultrasound.
2. Description of the Related Art
The use of ultrasound to therapeutically treat and evaluate bone injuries is known. Impinging ultrasonic pulses having appropriate parameters, e.g., frequency, pulse repetition, and amplitude, for suitable periods of time and at a proper external location adjacent to a bone injury has been determined to accelerate the natural healing of, for example, bone breaks and fractures.
U.S. Pat. No. 4,530,360 to Duarte describes a basic non-invasive therapeutic technique and apparatus for applying ultrasonic pulses from an operative surface placed on the skin at a location adjacent to a bone injury. To apply the ultrasound pulses during treatment an operator must manually hold the applicator in place until the treatment is complete.
The Duarte patent as well as U.S. Pat. No. 5,520,612 to Winder et al. describe ranges of RF signal for creating the ultrasound, ultrasound power density levels, ranges of duration for each ultrasonic pulse, and ranges of ultrasonic pulse frequencies.
U.S. Pat. No. 5,003,965 to Talish et al. relates to an ultrasonic body treatment system having a body-applicator unit connected a remote control unit by sheathed fiber optic lines. The signal controlling the duration of ultrasonic pulses and the pulse repetition frequency are generated apart from the body-applicator unit. Talish et al. also describes a mounting fixture for attaching the body-applicator unit to a patient so that the operative surface is adjacent the skin location.
While the systems described in these patents relate to therapeutic methods and apparatus for ultrasonic treatment of hard and soft issue injuries and defects, there is a need for ergonomically configured signal generators and transducers for the treatment of cartilage and/or osteochondral injuries and/or defects and/or for the treatment of cartilage/degenerative joint diseases, such as osteoarthritis (OA). Further, a need exists for an apparatus which optimizes the treatment of cartilage and/or osteochondral injuries and/or defects and/or the treatment of cartilage/degenerative joint diseases, such as osteoarthritis.
A cartilage and/or osteochondral injury and/or defect and/or degenerative joint disease, such as osteoarthritis, typically involves damage to the cartilage which lines articulating bones (articular cartilage), such as the bones of the knee, elbow, shoulder and ankle. Osteochondral injuries can be treated by chondral and/or osteochondral drilling causing blood flow at the site. The aim of chondral drilling is to stimulate cartilage regeneration as part of the healing process. However, the resulting nonhyaline or fibrocartilage produced is biomechanically inferior to articular cartilage, does not have comparable proteoglycan content, and may consist primarily of a thin unorganized layer of collagen. Further, it has been observed that degeneration of the new tissue generally occurs over time, requiring the need for additional reconstructive surgical treatment.
Other methods of treatment include: the transplantation of non-weight bearing cartilage to the injury and/or defect site; inducing a fracture at the injury and/or defect site; placing a carbon fiber matrix to induce cartilage formation; and autologous chondrocyte implantation (ACI). ACI entails removing chondrocytes capable of regenerating hyaline-like cartilage from the body and culturing them for several weeks. During the culture process, the number of cells increases approximately 15 times that of the original tissue sample. The cultured cells are then transplanted through an arthrotomy. A small piece of periosteum, the skin covering a bone, is taken from the patient's tibia. The periosteum is then sutured over the defect to provide a protective cover for the cultured cells. The cultured cells are injected under the periosteum into the defect where they will continue to multiply and produce a durable repair tissue. However, ACI increases the healing time since the chondrocytes need to be cultured before they are transplanted to the patient.
Therefore, there is a further need for a method and apparatus to stimulate cartilage regeneration which produces a repair tissue that is fibrocartilage or hyaline-like, and which is equivalent to articular cartilage in mechanical properties. There is also a need for repair tissue that is generally superior in mechanical properties to that generated using conventional techniques, as described above. Further still, a need also exists for an apparatus which stimulates cartilage regeneration and where the regenerated cartilage does not degenerate over time requiring additional treatment or reconstructive surgery. Further, there is a need for an apparatus which stimulates cartilage regeneration and significantly reduces the healing time.
For treatment of degenerative joint diseases such as osteoarthritis, some combination of symptom-modifying drug, physiotherapy with nonsteroidal antiinflammatories (NSAID's), bracing, weight loss, and/or reduced activity are initially used. However, while these approaches may control symptoms, they do not effectively address the underlying damage to connective tissue, such as cartilage. Moreover, the drugs used may cause severe side effects in some patients, which can result in hospitalization and, in some cases, death. It has been reported that an estimated 20,000 OA patients die each year in the United States from gastrointestinal complications associated with NSAID use. If symptoms remain after these treatments, then more invasive treatment methods are often used, such as injection of viscoelastic materials, arthroscopic surgery, or total joint replacement. There remains a need for additional methods and apparatus that treat and repair connective tissue damage, e.g. damage to cartilage, rather than simply control symptoms of osteoarthritis, and that do not have the side effects and/or tolerance problems associated with current pharmaceutical therapies.
However, injuries and pathologies of cartilage are not the only conditions of connective tissue requiring treatment that involve significant healing time. When ligament and tendons rupture the patients have pain and laxity of the joint or muscle. The current repair options available to the surgeon are to replace or reconstruct the damaged tissue with autograft or allograft tissue, augmentation of the tear surfaces with a device, or by fixation of the tissue with devices such as sutures or anchors, or to simply treat symptoms such as pain and inflammation, without resolving the underlying problem. Because of the risks associated with surgery, treatment options that do not necessarily involve surgery would be desirable. In addition, the repaired tissue is often not as strong as the original undamaged tissue, so that methods to increase repair tissue strength and decrease rehabilitation time would also be desirable. The success of therapies involving replacement or reconstructed tissue is often dependent on the body's ability to vascularize the tissue. Increased vascularization will lead to improved, faster healing, while insufficient vascularization can lead to necrosis of the tissue. Thus, methods for increasing vascularization in surgically repaired tissues would be advantageous.
In addition, in allograft or autograft replacement, the graft dies off and is subsequently repopulated and remodeled by infiltrating cells. This is a lengthy process during which time the graft loses strength and is at risk of rerupture or damage. This leads to lengthy rehabilitation times (e.g., a minimum of 6 months for anterior cruciate ligament (ACL) reconstruction). Inhibiting cell death within the graft via stimulation of blood vessel and tissue in-growth would therefore be desirable. This will lead to a faster and stronger repair and reduced rehabilitation time thus the patients will return to full function faster. The phenomenon of “bone tunnel widening” can often present a problem. Improved integration of bone/tissue/ligament interfaces would help to avoid the “windshield wiper effect” posited as a mechanism for bone tunnel widening.
Surgical methods are also typically required to repair menisci in the knee, for example. Increased vascularization of the avascular “white zone” of the menisci is desirable due to the stimulation in healing that results.
As explained above, the current treatments for many or most of these connective tissue injuries/pathologies are either surgical procedures including repair, reconstruction, augmentation, fixation and tissue resection, or the use of drug therapies that reduce the pain and inflammation. These procedures are usually followed by (or combined with) rehabilitation including physiotherapy which will include a series of stretching exercises with a gradual increase in range of motion and loading on the repair tissue. However, physiotherapy is inconvenient, time consuming and relatively expensive, which can lead to problems with patient compliance. There is thus a need in the art for methods of speeding healing and increasing vascularization that lend themselves to use by the patient at home, and do not require a significant amount of time each day.
It is often desirable to address problems such as laxity of joints by modifying tissues such that the collagenous components of connective tissues (joint capsules, tendons, ligaments) are induced to contract, a procedure often termed capsulorraphy. Applying thermal energy to collagen can cause an alteration of the molecular configuration resulting in shrinkage. This results in a shorter structure and a ‘tighter’ joint. However, the thermal energy incidentally may also damage the tissue resulting in loss of viability of cells, loss of blood supply and reduced mechanical integrity of the structure. Tissue shrinkage procedures have thus had difficulties resulting from decreased biomechanical integrity and long rehabilitation times due to slow healing. This has resulted in the ‘modified’ tissue being stretched back out prior to its healing and reestablishment of normal biomechanical strength, resulting in the loss of the benefit of the shrinkage procedure. This damage represents a significant disadvantage and has inhibited the use of capsulorraphy and related tissue shrinkage procedures. Faster post-shrinkage repair of tissue would minimize these difficulties and make the technique more widely applicable.
Tissue engineering involves the growth of cells on a scaffold in vitro (outside the body) to produce a graft for the repair of tissues within the body. One of the shortcomings of this approach is that it is not possible to grow a tissue-engineered material (implant, graft or organ) with a vascular supply in vitro. When the tissue-engineered material is placed into the body and stimulated with ultrasound functional blood vessels are stimulated to grow into the tissue-engineered material from the hosts own blood supply. This is a means of vascularization of this implanted material thus retaining the function and viability of the grafted material. There remains a need for methods and apparatus to achieve this vascularization of tissue engineered material.